1. Technical Field
This invention relates generally to microspheres capable of time releasing a drug and, more particularly to microspheres for implantation, injection, or other placement totally or partially within the body that are capable of near-linear controlled release of an antibiotic for an extended period of time, and to their methods of use for the treatment, deterrence and prevention of infections involving the body.
2. Description of the Prior Art
Historically, osteomyelitis treatment has consisted of debridement of infected tissues, irrigation with an antiseptic solution, and four to six weeks of parenteral antibiotic treatment. Due to poor penetration of the antibiotic into the infected bone site, high serum concentrations of the antibiotic need to be employed for extended periods of time in order to produce bactericidal levels within the bone tissue. These high serum levels can be associated with nephrotoxicity or ototoxicity, and can cause gastroinstestinal side effects. Due to the morbidity associated with high serum levels of antibiotics, many local delivery methods have been described including bone cement with antibiotics, collagen sponge with gentamycin, polymeric carriers with various antibiotics, and calcium sulfate carriers of antibiotics.
The need for a local drug delivery system to deliver antibiotics directly to the infection site led many physicians to mix antibiotics and polymethyl methacrylate (PMMA) bone cement into beads and place these beads into the debrided bone defect. PMMA has been used very successfully to deliver high levels of antibiotics locally without measurable systemic levels, but has several drawbacks. PMMA does not resorb and therefore a second surgery is required to remove the cement, as the cement is not biodegradable and may become a nidus for infection. Additionally, the elution of the antibiotic is nonlinear and most of the antibiotic mixed into the PMMA is permanently trapped in the cement. These drawbacks have led many researchers to develop bioresorbable delivery systems for local administration of antibiotics into infected tissue.
Infection may complicate any surgical treatment. Areas of high risk include fractures of bone treated with metal rods, plates or external fixators. The risk is particularly high if the fracture was open (compound fractures). Other surgical procedures are also at risk including vascular bypass surgery with the use of artificial graft material, general surgical procedures such as hernia repair and various procedures performed about the uterus and bladder. Once established, these infections are typically treated with surgical drainage and systemic antibiotics. Just as in the treatment of osteomyelitis, the treatment for infection may be prolonged, costly and may fail. There exists a need for a safe, effective local antibiotic delivery device that will improve healing and prevent complications.